Long-term behavioral effects of single or multiple doses of S-(+)-MDMA and d-methamphetamine were compared in rats. Rats in single dose studies received saline, S-(+)-MDMA (3 or 10 mg/kg), or d-methamphetamine (3 or 10 mg/kg), and rats in the multiple-dose studies received 4 injections of 10 mg/kg S-(+)-MDMA, d-methamphetamine, or saline, with injections given every 2 hours. 30 minutes post-drug, activity after a single dose of drug was videotaped for 20 minutes, and an observer scored the video for horizontal and vertical locomotion. In multiple dose studies, open field behavior was assessed 3 days, 1, 2, and 4 weeks post-drug. 3 days and 4 weeks after multiple doses, rats underwent passive avoidance learning, and 4 and 16 days post-drug, different groups of rats underwent active avoidance learning. In passive avoidance, the rats learned to avoid entering a chamber where foot shocks were delivered, and in active avoidance learning, rats learned to cross a barrier in order to avoid foot shock that was presaged by a cue (light onset). Rats underwent only one of the 3 behavioral tests. Unsurprisingly, both S-(+)-MDMA and d-methamphetamine increased locomotor activity, though some differences in horizontal activity were found between 3 and 10 mg/kg d-methamphetamine. Repeated doses of S-(+)-MDMA and d-methamphetamine reduced horizontal locomotion 3 days later, and S-(+)-MDMA reduced vertical locomotion, but activity levels returned to normal 1, 2 and 4 weeks post-drug. Repeated doses of either S-(+)-MDMA or d-methamphetamine failed to impair passive avoidance or active avoidance learning, whether assessed soon after treatment (3 or 4 days post-drug) or later (4 or 2 weeks (16 days) post-drug). The researchers did not report performing histological analyses of brain serotonin or dopamine content. The researchers conclude that presumably neurotoxic doses of S-(+)-MDMA or d-methamphetamine did not affect locomotor activity or learning in rats, a common finding (see Baggott et al. 2001 for review). If repeated (racemic) MDMA increases anxiety levels (Morley et al. 2001; McGregor et al. 2003, but see also Mechan et al. 2002), it is possible that repeated doses of S-(+)-MDMA may actually facilitate avoidance learning. A few studies have reported impaired learning of selected tasks, such as spatial navigation or novel object recognition (Broening et al. 2001; Morley-Fletcher et al. 2002; Williams et al. 2003), but no one has previously used avoidance learning tasks in studies of long-term effects of MDMA in rats. Humans consume racemic MDMA rather than S-(+)-MDMA, so generalizing to studies in humans should be done cautiously.